Estrogen replacement therapy has beneficial effects on heart disease risk factors. However, a large proportion of postmenopausal women are not compliant with therapeutic regimens. Phytoestrogens are naturally occurring compounds found in plants and soy products that have SERM-like effects. Although numerous studies have shown a beneficial effect of estrogens on lipids and lipoproteins, few examined other mechanisms by which phytoestrogens might exert a cardioprotective effect. Potential mechanisms include changes in homocysteine metabolism, inhibition in markers of inflammatory activity including interleukin-6 (IL- 6) and C-reactive protein (CRP), decreases in adhesion molecules such as E-selectin and decreases in obesity and body fat. Using new laboratory assays and previously collected data from 210 postmenopausal women in the Soy Health Effects (SHE) Study, this study will examine potential mechanisms other than lipids, by which phytoestrogens may reduce the risk of heart disease. The SHE Study is a randomized, double blind, placebo controlled study designed to determine the acceptability and benefits of a dietary supplement of phytoestrogen, specifically, genistein, on heart disease risk factors, bone density and psychosocial outcomes. Data was collected at screening, baseline, and periodic follow-ups over the course of two years. Funds are requested to assay homocysteine, IL-6, CRP, and E-selectin in frozen sera; and analyze data from SHE Study visits as related to the proposed hypotheses. Cross-sectional and longitudinal comparisons of treatment and placebo groups will be performed before and after adjustment and stratification for covariates. It is expected that women treated with phytoestrogens will have lower homocysteine, IL-6, CRP, E-selectin, and decreased obesity and fat mass over 2 years; that obesity and weight gain will be positively associated with homocysteine, IL-6, CRP, and E- selectin; and that there will be an interactive effect of phytoestrogen use and change in obesity on homocysteine, IL-6, CRP and E-selectin. Given that women can expect to live one-third of their lives after menopause, it is important to know whether and how phytoestrogens may modify cardiovascular disease mechanisms.